Suppression of epithelial to mesenchymal transition markers in mouse lens by a Smad7-based recombinant protein.
Suppression of epithelial to mesenchymal transition markers in mouse lens by a Smad7-based recombinant protein.
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DOI：
10.1016/j.cbi.2021.109495
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发表时间：
2021-08-01
影响因子：
5.1
通讯作者：
Petrash JM
中科院分区：
文献类型：
--
作者：
Hupy ML;Pedler MG;Shieh B;Wang D;Wang XJ;Petrash JM
白内障是一种混浊的眼晶状体，是导致视力受损的主要原因，也是全球最常见的外科手术之一。虽然白内障手术通常是安全有效的，但由于晶状体上皮细胞向间充质表型(EMT)的转变和晶状体后囊袋混浊，白内障手术可导致继发性晶状体异常。随着时间的推移，高达40%的白内障病例会发生后囊混浊(PCO)，这会带来额外的治疗成本，并降低患者的生活质量。研究表明，多囊卵巢综合征的发病部分是由转化生长因子-β驱动的，通过Smad共激活因子家族的作用发出信号，影响基因转录的变化。在本研究中，我们评估了Smad-7的能力，Smad-7是转化生长因子-β介导的Smad信号的典型抑制剂，它能够抑制与后发性白内障发病相关的晶状体上皮细胞的EMT反应。晶状体上皮细胞用一种细胞渗透型的Smad7变异体处理后，EMT标志物如α-平滑肌肌动蛋白和纤维连接蛋白的表达受到抑制。在小鼠白内障手术模型的囊袋中单独应用细胞渗透性Smad7变异体，导致编码α-平滑肌肌动蛋白和纤维连接蛋白的基因转录被抑制。这些结果表明，Smad7是一种很有前途的生物治疗剂，可以预防或大幅降低白内障手术后后发性白内障的发生率。
Cataracts, a clouding of the eye lens, are a leading cause of visual impairment and are responsible for one of the most commonly performed surgical procedures worldwide. Although generally safe and effective, cataract surgery can lead to a secondary lens abnormality due to transition of lens epithelial cells to a mesenchymal phenotype (EMT) and opacification of the posterior lens capsular bag. Occurring in up to 40% of cataract cases over time, posterior capsule opacification (PCO) introduces additional treatment costs and reduced quality of life for patients. Studies have shown that PCO pathogenesis is driven in part by TGF-β, signaling through the action of the family of Smad coactivators to effect changes in gene transcription. In the present study, we evaluated the ability of Smad-7, a well characterized inhibitor of TGF-β -mediated Smad signaling, to suppress the EMT response in lens epithelial cells associated with PCO pathogenesis. Treatment of lens epithelial cells with a cell-permeable form of Smad7 variant resulted in suppressed expression of EMT markers such as alpha smooth muscle actin and fibronectin. A single application of cell-permeable Smad7 variant in the capsular bag of a mouse cataract surgery model resulted in suppression of gene transcripts encoding alpha smooth muscle actin and fibronectin. These results point to Smad7 as a promising biotherapeutic agent for prevention or substantial reduction in the incidence of PCO following cataract surgery.
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影响因子：
4.4
作者：
Jiang J;Shihan MH;Wang Y;Duncan MK
通讯作者：
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影响因子：
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作者：
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